rs1525677

Positions:

• chr7-110662639-T-C
• chr7-110662639-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 7-110662639-T-C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,072 control chromosomes in the GnomAD database, including 10,493 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10493 hom., cov: 33)
• Consequence: IMMP2L NM_032549.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

Genes affected

IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMP2L	NM_032549.4			downstream_gene_variant		ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7			downstream_gene_variant		1	NM_032549.4	ENSP00000384966	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54333 AN: 151954 Hom.: 10497 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54369 AN: 152072 Hom.: 10493 Cov.: 33 AF XY: 0.347 AC XY: 25823 AN XY: 74328

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.351

Alfa AF: 0.307 Hom.: 4186

Bravo AF: 0.367

Asia WGS AF: 0.163 AC: 568 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1525677; hg19: chr7-110302695;